Flow Synthesis of Diaryliodonium Triflates - The Journal of Organic

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Cite This: J. Org. Chem. 2017, 82, 11735-11741

Flow Synthesis of Diaryliodonium Triflates Gabriele Laudadio,† Hannes P. L. Gemoets,† Volker Hessel, and Timothy Noel̈ * Department of Chemical Engineering and Chemistry, Micro Flow Chemistry & Process Technology, Eindhoven University of Technology, Den Dolech 2, 5612 AZ Eindhoven, The Netherlands S Supporting Information *

ABSTRACT: A safe and scalable synthesis of diaryliodonium triflates was achieved using a practical continuous-flow design. A wide array of electron-rich to electron-deficient arenes could readily be transformed to their respective diaryliodonium salts on a gram scale, with residence times varying from 2 to 60 s (44 examples).

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INTRODUCTION In recent years, the applications of aryl electrophile sources, such as hypervalent iodinated compounds, have become increasingly important in synthetic organic chemistry.1 In particular, diaryl-λ3-iodanes, also known as diaryliodonium salts, have been extensively used in numerous arylation procedures.2 Such diaryliodonium salts can be considered as both strong electrophiles and powerful oxidants, which allows chemists to reach higher oxidation states with Pd or Cu complexes and to carry out the targeted transformations at milder reaction conditions.3 Furthermore, diaryliodonium salts can be used as an electrophilic aryl source to couple with a wide variety of nucleophiles, allowing the preparation of sulfides,4 ethers,5 amines,6 esters,7 and nitro compounds8 as well as the αarylation on enolates.9 Given the apparent importance of diaryliodonium salts, many syntheses have been developed to prepare these compounds.10 The most practical reaction conditions involve the reaction of iodoarenes with a suitable oxidant to give I+III followed by a ligand exchange with an arene. An improved one-pot version was developed by Olofsson et al. using meta-chloroperbenzoic acid (m-CPBA) as the oxidant and trifluoromethanesulfonic acid (TfOH) to yield diaryliodonium triflates directly.11 However, such oxidative reaction conditions are typically very exothermic and thus represent a substantial safety risk when carried out on a large scale. Herein, we present a flow synthesis of diaryliodonium triflates which is fast and scalable and provides a broad substrate scope.

cross-micromixer and microreactor were placed inside. High vacuum was applied to the system in order to create adiabatic conditions (for more details about the setup, see the Supporting Information). Assuming full conversion, we calculated the reaction enthalpy using the following equation, ΔHR = m × Cp × ΔT, where m and Cp are the mass and the heat capacity of the solvent, respectively (Cp values of substrates were neglected, which is fair given the dilution). A thermocouple was connected to the T-mixer at the end of the microreactor, which allowed us to have in-line temperature measurements. The calibration of the adiabatic system was performed using the well-known neutralization reaction of sodium hydroxide with hydrochloric acid.13 Next, we carried out the synthesis of diphenyliodonium triflate and di-ptolyliodonium triflate in the adiabatic microfluidic device, and ΔT values were measured (reactions were performed three times each). With the Cp value of DCE known (Cp = 129.4 J· mol−1·K−1),14 we were able to directly calculate the respective enthalpy values. Interestingly, very high ΔHR values between −160 and −180 kJ/mol were observed, highlighting the need for a safe and reliable method to scale the reaction conditions (Scheme 1).15 Such exothermic transformations can be carried out safely in continuous-flow microreactors as the microenvironment results in an excellent heat dissipation rate.16 We commenced our investigations by designing a suitable continuous-flow setup (Figure 1). Our design consists of three individual feeds that allow separation of the hazardous reagents and control of the reaction stoichiometry by adjusting the individual flow rates. The different reagent streams were merged in a cross-micromixer and subsequently introduced in a perfluoroalkoxy capillary reactor (PFA, 750 μm i.d., 0.1−3.0 mL). To avoid microreactor clogging, the mixer and reactor

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RESULTS AND DISCUSSION To quantify the thermodynamic data of highly exothermic reactions, reaction calorimetry is typically used.12 In order to rapidly determine the unknown reaction enthalpy (ΔHR) of the diaryliodonium salt synthesis, we developed an operationally simple adiabatic continuous-flow device that allowed us to calculate ΔHR values via in-line ΔT measurements (see Scheme 1c). Hereto, a custom-made glass tube was designed, and the © 2017 American Chemical Society

Special Issue: Hypervalent Iodine Reagents Received: June 13, 2017 Published: July 11, 2017 11735

DOI: 10.1021/acs.joc.7b01346 J. Org. Chem. 2017, 82, 11735−11741

Article

The Journal of Organic Chemistry Scheme 1. (A) Advantages and Disadvantages of Diaryliodonium Salts, (B) Enthalpy Measurement of the Diaryliodonium Salt Synthesis in an Adiabatic Microreactor, and (C) Flow Setup Used for the Enthalpy Measurements

Figure 2. Comparison of the solids obtained after precipitation of di-ptolyliodonium triflate (3a) produced either in batch (left) or flow (right).

Table 1. Scope of Diaryliodonium Triflates Using ElectronNeutral and Electron-Rich Aryl Iodidesa

Figure 1. Schematic representation of the microflow setup.

were submerged in an ultrasonic bath.17 The reaction between 4-iodotoluene (1a) and toluene (2a) in the presence of mCPBA and TfOH was selected as the benchmark for our reaction optimization studies (see the Supporting Information). Optimal reaction conditions were obtained with 1.1 equiv of 2a and m-CPBA, and 2 equiv of TfOH and dichloroethane (DCE) as the solvent in a 100 μL microreactor. The reaction was remarkably fast and was completed within 2 s residence time. Notably, the desired di-p-tolyliodonium triflate 3a could be obtained on a gram scale (2.04 g, 89%) in excellent yield as pure and simple to handle crystals (Figure 2). Analogous batch experiments resulted in a lower yield (69% yield) of 3a as an inferior-quality powder precipitate. With the optimized conditions in hand, we sought to demonstrate the generality of our flow protocol (Table 1). Within a 2 s residence time, a diverse set of both symmetrical and unsymmetrical diaryliodonium triflates was synthesized in fair to excellent yield on a gram scale (5−10 mmol scale).

a

Reaction conditions. Feed 1: 5.0 mmol of aryl iodide (1), 5.5 mmol of arene (2) in 25 mL of DCE. Feed 2: 5.5 mmol of m-CPBA in 25 mL of DCE. Feed 3: 10 mmol of TfOH in 50 mL of DCE. Throughput distribution, feed 1/feed 2/feed 3 was 1:1:2. b10 mmol scale reaction.

Symmetrical diaryliodonium triflates were readily produced in good to excellent yields (3a−3c). Using different (hetero)arenes, unsymmetrical diaryliodonium salts were synthesized (3d, 3e). Furthermore, the use of sterically hindered mesitylene was well-tolerated, providing access to a diverse set of aryl mesityliodonium triflates (3f−3p). These compounds are of high interest in cross-coupling and C−H arylation chemistry because they allow selective transfer of the functionalized aryl groups to the substrate. Aryl iodides bearing strong electron11736

DOI: 10.1021/acs.joc.7b01346 J. Org. Chem. 2017, 82, 11735−11741

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The Journal of Organic Chemistry donating substituents (e.g., anisoles) or electron-rich heteroaromatic iodides (e.g., thiophene) were incompatible with the reaction conditions. However, these diaryliodonium triflates could be accessed when using the mesityl iodide with the corresponding (hetero)arenes, albeit in a lower yield (3q and 3r). Aryl iodides with electron-withdrawing functional groups proved particularly challenging. However, after a minor reoptimization of the reaction conditions (see the Supporting Information), it was found that these compounds could be obtained in good yields by increasing the reactor volume to 3 mL and using an excess of m-CPBA (1.3 equiv) and TfOH (3.0 equiv). Aryl iodides bearing ortho, meta, and para electronwithdrawing substituents (e.g., halogens, nitro, esters, ketones) were all well-tolerated, yielding the targeted diaryliodonium triflates in synthetically useful yields (32−90% yield) (Table 2). Also, 3-iodopyridine (3x and 3ai) and 1-iodoanthraquinone (3s) could be subjected to the flow conditions, resulting in the desired compounds in fair yields (19−47% yield). Finally, with the aim of developing a flow protocol utilizing cheap and easily available starting materials, we chose to oxidize simple arenes using molecular iodine to yield the corresponding symmetrical diaryliodonium triflates. Optimal results were

obtained using iodine as the limiting reagent along with 3 equiv of m-CPBA, 4.1−10 equiv of arene, and 5 equiv of TfOH (see the Supporting Information). Moderate to excellent yields were obtained for the synthesis of symmetrical diaryliodonium salts (38−90%) (Table 3). In most cases, the para−paraTable 3. Scope of Symmetric Diaryliodonium Triflates Derived from Arenes and Molecular Iodinea

Table 2. Scope of Diaryliodonium Triflates with ElectronDeficient Substratesa a

Reaction conditions. Feed 1: 2.0 mmol of 4, 10 equiv of 2 in 10 mL of DCE. Feed 2: 6.0 mmol of m-CPBA in 10 mL of DCE. Feed 3: 10 mmol of TfOH in 10 mL of DCE. Syringe pumps were used to add reagents to the reactor. Throughput distribution, feed 1/feed 2/feed 3 was 1:1:2. b4.1 equiv of arene was used. cSelectivity at room temperature: ortho−para 90%, para−para 5%, and ortho−ortho 5%. d Selectivity at 0 °C: ortho−para >96%.

substituted diaryliodonium analogues were obtained as the only regioisomer. However, when using toluene as the substrate, several other regioisomers were obtained with the ortho−para isomer being the most abundant (3ak). However, the selectivity could be completely tuned toward the ortho−para isomer by decreasing the reaction temperature to 0 °C.

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CONCLUSIONS In summary, we have developed a fast, scalable, and safe continuous-flow protocol to prepare various symmetrical and unsymmetrical diaryliodonium triflates. Our protocol displayed a broad substrate scope of electron-rich to electron-deficient substrates (44 examples, yields up to 92%). Notably, the reaction could be completed in a matter of seconds, allowing the preparation the diaryliodonium triflates on a gram scale with excellent purity in a time-efficient fashion. We believe that the developed flow protocol will find widespread use in both academia and industry given the synthetic relevance of diaryliodonium salts.

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EXPERIMENTAL SECTION

All reagents and solvents were used as received without further purification. All capillary tubing and microfluidic fittings were purchased from IDEX Health & Science. Used syringes were from BD Discardit II or NORM-JECT. Syringe pumps were purchased from Chemix Inc. model Fusion 200 Touch. Used ultrasonicator was VWR USC300T. 1H (400 MHz), 13C (100 MHz), and 19F (376 MHz) NMR spectra were recorded at ambient temperature using a Bruker Avance 400 or Mercury 400 spectrometer. 1H NMR spectra are

a

Reaction conditions. Feed 1: 5.0 mmol of 1, 5.5 mmol of 2 in 25 mL of DCE. Feed 2: 6.5 mmol of m-CPBA in 25 mL of DCE. Feed 3: 15 mmol of TfOH in 50 mL of DCE. Throughput distribution, feed 1/ feed 2/feed 3 was 1:1:2. 11737

DOI: 10.1021/acs.joc.7b01346 J. Org. Chem. 2017, 82, 11735−11741

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The Journal of Organic Chemistry reported in parts per million (ppm) downfield relative to CDCl3 (7.26 ppm) and DMSO-d6 (2.50 ppm); all 13C{1H} NMR spectra are reported in ppm relative to CDCl3 (77.2 ppm) and DMSO-d6 (39.52 ppm). HRMS (ESI/APCI multimode ionization source, TOF-MSD analyzer) was measured with direct infusion in a 50:50 flow of 5 mM NH4OAc in water/MeOH. NMR data were processed using the MestReNova 9.0.1 software package. Known products were characterized by comparison to the corresponding 1H NMR and 13C NMR from literature. Melting points were determined with a Buchi B540 capillary melting point apparatus in open capillaries and are uncorrected. The names of all products were generated using the PerkinElmer ChemBioDraw Ultra v.12.0.2 software package. General Procedure for the Diaryliodonium Salt Synthesis with Electron-Neutral and Electron-Rich Substrates (GP1). A 25 mL oven-dried volumetric flask was charged with 4-iodotoluene (1a, 1.09 g, 5.0 mmol) and toluene (2a, 506 mg, 5.5 mmol). Next, a second 25 mL oven-dried volumetric flask was charged with metachloroperbenzoic acid (≤77%) (1.24 g, 5.5 mmol). Both the flasks were fitted with a septum and were degassed by alternating vacuum and argon backfill. Dichloroethane was added via syringe to make a 25.0 mL solution in both flasks. Both the solutions were charged in 30 mL NORM-JECT syringes and were fitted to a single syringe pump. Afterwards, a 50 mL oven-dried volumetric flask fitted with a septum and was degassed by alternating vacuum and argon backfill and charged with 20 mL of dichloroethane. Trifluoromethanesulfonic acid (0.9 mL, 10.0 mmol) was added carefully with a syringe, and dichloroethane was added via syringe to make a 50.0 mL solution. The solution was charged in a 60 mL NORM-JECT syringe and fitted to a second syringe pump. All syringes were connected to a PEEK crossmixer (500 μm i.d.) and subsequently connected to the inlet of the 0.1 mL PFA capillary tubing (750 μm i.d.). The cross-mixer and microreactor were submerged in a sonication bath, and sonication was applied during operation. The first syringe pump (containing two syringes) was operated at 2 × 0.75 mL/min, and the second syringe pump was operated at 1.5 mL/min (total 3 mL/min flow rate, 2 s residence time). The outlet of the reactor was fitted to an argon-filled round-bottom flask with septum via a needle connection. An argonfilled balloon was attached in order to ensure a constant pressure. The reaction mixture was evaporated under reduced pressure at the rotavap. Residue was dissolved in diethyl ether and evaporated again at the rotavap. This procedure was repeated three times, and then the residue was dissolved in a minimum amount of acetone, followed by addition of diethyl ether until a cloudy solution was obtained. Next, the resulting mixture was kept in the freezer (−26 °C) overnight. Formed crystals were filtered off and washed with a minimum of diethyl ether. General Procedure for the Diaryliodonium Salt Synthesis with Electron-Deficient Substrates (GP2). A 25 mL oven-dried volumetric flask was charged with 4-iodonitrobenzene (1b, 1.25 g, 5.0 mmol) and mesitylene (2b, 0.76 mL, 5.5 mmol). Next, a second 25 mL oven-dried volumetric flask was charged with meta-chloroperbenzoic acid (≤77%) (1.5 g, 6.5 mmol). Both the flasks were fitted with a septum and were degassed by alternating vacuum and argon backfill. Dichloroethane was added via syringe to make a 25.0 mL solution in both flasks. Both the solutions were charged in 30 mL NORM-JECT syringes and were fitted to a single syringe pump. Afterwards, a 50 mL oven-dried volumetric flask was fitted with a septum and was degassed by alternating vacuum and argon backfill and charged with 40 mL of dichloroethane. Trifluoromethanesulfonic acid (1.3 mL, 15 mmol) was added carefully with a syringe, and dichloroethane was added via syringe to make a 50.0 mL solution. The solution was charged in a 60 mL NORM-JECT syringe and fitted to a second syringe pump. All syringes were connected to a PEEK cross-mixer (500 μm i.d.) and subsequently connected to the inlet of the 3.0 mL PFA capillary tubing (750 μm i.d.). The cross-mixer and microreactor were submerged in a sonication bath, and sonication was applied during operation. The first syringe pump (containing two syringes) was operated at 2 × 0.75 mL/ min, and the second syringe pump was operated at 1.5 mL/min (total 3 mL/min flow rate, 60 s residence time). The outlet of the reactor was fitted to an argon-filled round-bottom flask with septum via a

needle connection. An argon-filled balloon was attached in order to ensure a constant pressure. The reaction mixture was evaporated under reduced pressure at the rotavap. Residue was dissolved in diethyl ether and evaporated again at the rotavap. This procedure was repeated three times, and then the residue was dissolved in a minimum amount of acetone, followed by addition of diethyl ether until a cloudy solution was obtained. Next, the resulting mixture was kept in the freezer (−26 °C) overnight. Formed crystals were filtered off and washed with a minimum of diethyl ether. General Procedure for the Diaryliodonium Salt Synthesis with Iodine (GP3). A 10 mL oven-dried volumetric flask was charged with iodine (4, 507 mg, 2 mmol) and the arene (2, 8.2−20 mmol). Next, a second 10 mL oven-dried volumetric flask was charged with meta-chloroperbenzoic acid (≤77%) (1.5 g, 6 mmol). Both the flasks were fitted with a septum and were degassed by alternating vacuum and argon backfill. Dichloroethane was added via syringe to make a 10 mL solution in both flasks. Both the solutions were charged in 10 mL NORM-JECT syringes and were fitted to a single syringe pump. Afterwards, a 25 mL oven-dried volumetric flask was fitted with a septum and was degassed by alternating vacuum and argon backfill and charged with around 15 mL of dichloroethane. Trifluoromethanesulfonic acid (0.9 mL, 10.0 mmol) was added carefully with a syringe, and dichloroethane was added via syringe to make a 20.0 mL solution. The solution was charged in a 20 mL NORM-JECT syringe and fitted to a second syringe pump. All syringes were connected to a PEEK cross-mixer (500 μm i.d.) and subsequently connected to the inlet of the 3 mL PFA capillary tubing (750 μm i.d.). The cross-mixer and microreactor were submerged in a sonication bath, and sonication was applied during operation. The first syringe pump (containing two syringes) was operated at 2 × 0.75 mL/min, and the second syringe pump was operated at 1.5 mL/min (total 3 mL/min flow rate, 60 s residence time). The outlet of the reactor was fitted to an argon-filled round-bottom flask with septum via a needle connection. An argonfilled balloon was attached in order to ensure a constant pressure. The reaction mixture was evaporated under reduced pressure at the rotavap. Residue was dissolved in diethyl ether and evaporated again at the rotavap. This procedure was repeated five times, and then the residue was dissolved in a minimum amount of acetone, followed by addition of diethyl ether until a cloudy solution was obtained. Next, the resulting mixture was kept in the freezer (−26 °C) overnight. Formed crystals were filtered off and washed with a minimum of diethyl ether. Di-p-tolyliodonium Trifluoromethanesulfonate (3a).18 GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as gray solids (2.04g, 89%): mp 131−133 °C (lit.18 121−123 °C); 1H NMR (400 MHz, DMSO-d6) δ 8.15−8.05 (m, 4H), 7.31 (d, J = 8.1 Hz, 4H), 2.32 (s, 6H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 142.5, 135.0, 132.3, 120.8 (q, J = 322.3 Hz), 113.1, 20.8. Diphenyliodonium Trifluoromethanesulfonate (3b).19 GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as off-white solids (1.89 g, 88%). GP3 was used on a 4 mmol scale. Purification by recrystallization in diethyl ether afforded the product as off-white solids (1.55 g, 90%): mp 169− 173 °C (lit.19 172−174 °C); 1H NMR (400 MHz, DMSO-d6) δ 8.27 (d, J = 8.0 Hz, 4H), 7.64 (t, J = 7.4 Hz, 2H), 7.52 (t, J = 7.7 Hz, 4H); 13 C{1H} NMR (101 MHz, DMSO-d6) δ 135.2, 132.1, 131.8, 120.8 (q, J = 322.3 Hz), 116.5. Bis(4-fluorophenyl)iodonium Trifluoromethanesulfonate (3c).2c GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as gray solids (1.35 g, 58%). GP3 was used on a 4 mmol scale. Purification by recrystallization in diethyl ether afforded the product as gray solids (1.34 g, 72%): mp 168−170 °C (lit.2c 168−170 °C); 1H NMR (400 MHz, DMSO-d6) δ 8.39−8.22 (m, 4H), 7.42 (t, J = 8.9 Hz, 4H); 13C{1H} NMR (101 MHz, DMSOd6) δ 164.4 (d, J = 251.5 Hz), 138.4 (d, J = 9.1 Hz), 122.7 (q, J = 322.6 Hz), 119.8, 119.6, 111.6 (d, J = 3.0 Hz); 19F NMR (376 MHz, DMSOd6) δ −77.75, −106.60 (tt, J = 9.0, 5.0 Hz). (4-Iodophenyl)(phenyl)iodonium Trifluoromethanesulfonate (3d).19 GP1 was used on a 5 mmol scale. Purification by 11738

DOI: 10.1021/acs.joc.7b01346 J. Org. Chem. 2017, 82, 11735−11741

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The Journal of Organic Chemistry

°C (lit.20 167−168 °C); 1H NMR (400 MHz, CDCl3) δ 7.50−7.38 (m, 3H), 7.17 (td, J = 7.7, 7.1, 2.0 Hz, 1H), 7.11 (s, 2H), 2.60 (s, 9H), 2.36 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 144.8, 142.7, 140.4, 133.7, 132.7, 132.6, 130.9, 130.0, 120.5 (q, J = 321.8 Hz), 119.7, 115.8, 27.1, 25.05, 21.2. (2-Fluorophenyl)(mesityl)iodonium Trifluoromethanesulfonate (3m).21 GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as white solids (907 mg, 37%): mp 157−159 °C (lit.21 161−162 °C); 1H NMR (399 MHz, CDCl3) δ 7.81 (ddd, J = 7.8, 5.8, 1.6 Hz, 1H), 7.59 (dddd, J = 8.6, 7.2, 5.4, 1.6 Hz, 1H), 7.35−7.19 (m, 2H), 7.08 (s, 2H), 2.68 (s, 6H), 2.34 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 160.5 (d, J = 252.1 Hz), 144.6, 142.7, 136.1, 135.2 (d, J = 8.0 Hz), 130.6, 127.6 (d, J = 3.3 Hz), 121.5, 117.6 (d, J = 21.8 Hz), 98.0 (d, J = 23.9 Hz), 27.1, 21.2; 19F NMR (376 MHz, CDCl3) δ −78.35, −95.37 to −96.24 (m). Mesityl(m-tolyl)iodonium Trifluoromethanesulfonate (3n).21 GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as off-white solids (1.94 g, 80%): mp 169− 171 °C (lit.21 171−172 °C); 1H NMR (399 MHz, CDCl3) δ 7.58 (s, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.33 (d, J = 7.5 Hz, 1H), 7.26 (t, J = 7.8 Hz, 1H), 7.10 (s, 2H), 2.62 (s, 6H), 2.35 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.6, 143.3, 142.7, 133.6, 132.9, 132.1, 130.5, 129.9, 120.5 (q, J = 320.5 Hz), 120.2, 111.6, 27.3, 21.5, 21.3. (3,5-Dimethylphenyl)(mesityl)iodonium Trifluoromethanesulfonate (3o). GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as off-white solids (1.80 g, 72%): mp 200−203 °C; 1H NMR (399 MHz, CDCl3) δ 7.28 (s, 2H), 7.14 (s, 1H), 7.11 (s, 2H), 2.63 (s, 6H), 2.36 (s, 3H), 2.30 (s, 6H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.6, 142.9, 142.7, 134.0, 130.6, 130.5, 120.7 (q, J = 321.3 Hz), 120.0, 111.4, 27.3, 21.5, 21.3; HRMS (ESI) calcd for C17H20I [M − OTf]+ 351.0604, found 351.0616. Dimesityliodonium Trifluoromethanesulfonate (3p).19 GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as brown solids (1.44 g, 56%). GP3 was used on a 4 mmol scale. Purification by recrystallization in diethyl ether afforded the product as brown solids (1.08 g, 53%): mp 183− 186 °C (lit.19 187−188 °C); 1H NMR (400 MHz, CDCl3) δ 7.05 (s, 4H), 2.51 (s, 12H), 2.33 (s, 6H); 13C{1H} NMR (101 MHz, CDCl3) δ 144.0, 142.4, 131.1, 117.4, 26.3, 21.1. Mesityl(4-methoxyphenyl)iodonium Trifluoromethanesulfonate (3q).2c GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as dark gray solids (502 mg, 20%): mp 148−150 °C (lit.2c 148−151 °C); 1H NMR (400 MHz, CDCl3) δ 7.69−7.57 (m, 2H), 7.10 (s, 2H), 6.98−6.85 (m, 2H), 3.82 (s, 3H), 2.64 (s, 6H), 2.35 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 162.8, 144.7, 142.4, 135.5, 130.6, 121.0, 118.3, 99.9, 55.9, 27.2, 21.3. Mesityl(thiophen-2-yl)iodonium Trifluoromethanesulfonate (3r). GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as light brown solids (1.20 g, 50%): mp 160−162 °C; 1H NMR (400 MHz, CDCl3) δ 7.73 (dd, J = 3.8, 1.2 Hz, 1H), 7.61 (dd, J = 5.4, 1.2 Hz, 1H), 7.11−7.04 (m, 3H), 2.73 (s, 6H), 2.33 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 144.5, 141.7, 139.7, 135.8, 130.6, 129.8, 125.7, 120.3 (q, J = 319.6 Hz), 94.5, 27.2, 21.2; HRMS (ESI) calcd for C13H14IS [M − OTf]+ 328.9855, found 328.9857. (9,10-Dioxo-9,10-dihydroanthracen-1-yl)(p-tolyl)iodonium Trifluoromethanesulfonate (3s). GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as light gray solids (1.29 g, 45%): mp 225−230 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.47−8.41 (m, 1H), 8.39 (dd, J = 7.0, 2.0 Hz, 1H), 8.30 (dd, J = 7.2, 1.9 Hz, 1H), 8.25 (d, J = 8.3 Hz, 2H), 8.09 (qd, J = 7.3, 1.7 Hz, 2H), 8.02 (t, J = 8.0 Hz, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.36 (dd, J = 8.2, 1.0 Hz, 1H), 2.52 (s, 3H); 13C{1H} NMR (101 MHz, DMSO) δ 185.3, 181.2, 144.9, 138.1, 137.3, 136.9, 136.3, 135.7, 133.7, 133.3, 132.2, 131.9, 130.4, 129.9, 128.2, 127.8, 114.7, 108.4, 21.7; HRMS (ESI) calcd for C21H14IO2 [M − OTf]+ 425.0033, found 425.0030.

recrystallization in diethyl ether afforded the product as off-white solids (2.09 g, 75%): mp 144−148 °C (lit.19 146−148 °C); 1H NMR (400 MHz, DMSO-d6) δ 8.24 (d, J = 7.0 Hz, 2H), 8.00 (d, J = 8.5 Hz, 2H), 7.90 (d, J = 8.5 Hz, 2H), 7.68 (t, J = 7.4 Hz, 1H), 7.54 (t, J = 7.8 Hz, 2H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 140.39, 136.75, 135.16, 132.14, 131.80, 120.67 (q, J = 322.4 Hz), 116.67, 115.83, 100.28. Phenyl(thiophen-2-yl)iodonium Trifluoromethanesulfonate (3e).2c GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as light brown solids (937 mg, 43%): mp 143−146 °C (lit.2c 144−146 °C); 1H NMR (400 MHz, DMSO-d6) δ 8.29−8.21 (m, 2H), 8.07 (dd, J = 3.8, 1.3 Hz, 1H), 7.97 (dd, J = 5.3, 1.3 Hz, 1H), 7.71−7.63 (m, 1H), 7.58−7.47 (m, 2H), 7.18 (dd, J = 5.3, 3.8 Hz, 1H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 140.9, 137.8, 135.1, 132.6, 132.2, 130.1, 121.2 (q, J = 322.2 Hz), 119.8, 101.2. Mesityl(phenyl)iodonium Trifluoromethanesulfonate (3f).20 GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as off-white solids (2.05g, 87%): mp 148− 150 °C (lit.20 137−138 °C); 1H NMR (400 MHz, DMSO-d6) δ 8.06− 7.94 (m, 2H), 7.69−7.60 (m, 2H), 7.51 (t, J = 7.8 Hz, 2H), 7.22 (s, 2H), 2.62 (s, 6H), 2.29 (s, 3H); 13C{1H} NMR (101 MHz, DMSOd6) δ 143.1, 141.6, 134.5, 131.9, 129.8, 122.6, 120.7 (q, J = 322.3 Hz), 114.5, 26.3, 20.5. Mesityl(p-tolyl)iodonium Trifluoromethanesulfonate (3g).20 GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as white solids (2.07g, 85%): mp 181−183 °C (lit.20 183−184 °C); 1H NMR (400 MHz, DMSO- d6) δ 7.87 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.1 Hz, 2H), 7.21 (s, 2H), 2.60 (s, 6H), 2.33 (s, 3H), 2.29 (s, 3H); 13C{1H} NMR (101 MHz, DMSO) δ 143.0, 142.2, 141.4, 134.5, 132.5, 129.7, 122.7, 110.9, 26.3, 20.8, 20.5. (4-Acetamidophenyl)(mesityl)iodonium Trifluoromethanesulfonate (3h). GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as off-white solids (741 mg, 28%): mp 136−138 °C; 1H NMR (399 MHz, DMSOd6) δ 10.28 (s, 1H), 7.93 (d, J = 8.7 Hz, 2H), 7.66 (d, J = 8.6 Hz, 2H), 7.20 (s, 2H), 2.60 (s, 6H), 2.28 (s, 3H), 2.05 (s, 3H); 13C{1H} NMR (100 MHz, DMSO) δ 169.5, 143.4, 142.8, 141.8, 136.3, 130.2, 123.4, 122.7, 122.0, 106.3, 26.7, 24.6, 21.0; HRMS (ESI) calcd for C17H19F3INO [M − OTf]+ 380.0506, found 380.0514. (4-Fluorophenyl)(mesityl)iodonium Trifluoromethanesulfonate (3i). 20 GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as gray solids (1.96 g, 80%): mp 173−176 °C (lit.20 177−178 °C); 1H NMR (400 MHz, CDCl3) δ 7.73 (dd, J = 8.5, 4.7 Hz, 2H), 7.10 (d, J = 4.9 Hz, 4H), 2.63 (s, 6H), 2.35 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3 δ 164.7 (d, J = 255.0 Hz), 144.6, 142.5, 135.7 (d, J = 8.7 Hz), 130.5, 121.2, 120.3 (q, J = 319.8 Hz), 119.8 (d, J = 22.9 Hz), 105.3 (d, J = 3.4 Hz), 27.2, 21.3; 19F NMR (376 MHz, CDCl3) δ −78.40, −106.01 (ddd, J = 12.8, 8.2, 4.7 Hz). (4-Iodophenyl)(mesityl)iodonium Trifluoromethanesulfonate (3j). GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as dark white solids (2.24 g, 75%): mp 193−195 °C; 1H NMR (400 MHz, DMSO-d6) δ 7.86 (d, J = 8.5 Hz, 2H), 7.71 (d, J = 8.5 Hz, 2H), 7.23 (s, 2H), 2.58 (s, 6H), 2.30 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 143.5, 141.7, 141.6, 140.4, 136.8, 136.0, 129.9, 129.82, 122.7, 122.6, 116.3 (q, J = 397.4 Hz), 99.7, 26.3, 20.5. [1,1′-Biphenyl]-4-yl(mesityl)iodonium Trifluoromethanesulfonate (3k). GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as pale green solids (1.67 g, 61%): mp 185−187 °C; 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 8.6 Hz, 2H), 7.63−7.58 (m, 2H), 7.54−7.39 (m, 5H), 7.14 (s, 2H), 2.67 (s, 6H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 145.4, 144.9, 142.7, 138.5, 133.5, 131.1, 130.7, 129.3, 129.0, 127.3, 120.5, 109.9, 27.4, 21.3; HRMS (ESI) calcd for C21H20I [M − OTf]+ 399.0604, found 399.0585. Mesityl(o-tolyl)iodonium Trifluoromethanesulfonate (3l).20 GP1 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as white solids (2.09g, 86%): mp 170−172 11739

DOI: 10.1021/acs.joc.7b01346 J. Org. Chem. 2017, 82, 11735−11741

Article

The Journal of Organic Chemistry Bis(4-chlorophenyl)iodonium Trifluoromethanesulfonate (3t).2c GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as white solids (1.57 g, 63%). GP3 was used on a 4 mmol scale. Purification by recrystallization in diethyl ether afforded the product as white solids (1.32 g, 66%): mp 183−187 °C (lit.2c 185−186 °C); 1H NMR (400 MHz, DMSO-d6) δ 8.42−8.08 (m, 4H), 7.75−7.47 (m, 4H); 13C{1H} NMR (101 MHz, DMSO) δ 137.9, 137.4, 132.3, 115.2. Bis(4-bromophenyl)iodonium Trifluoromethanesulfonate (3u).2c GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as white solids (2.37 g, 81%). GP3 was used on a 4 mmol scale. Purification by recrystallization in diethyl ether afforded the product as white solids (1.46 g, 62%): mp 183−188 °C (lit.2c 185−190 °C); 1H NMR (400 MHz, DMSO-d6) δ 8.17 (d, J = 8.6 Hz, 4H), 7.77 (d, J = 8.6 Hz, 4H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 137.0, 134.7, 126.3, 115.4. (4-Bromophenyl)(4-chlorophenyl)iodonium Trifluoromethanesulfonate (3v). GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as white needles (2.01g, 74%): mp 201−204 °C; 1H NMR (399 MHz, DMSO-d6) δ 8.31−8.23 (m, 2H), 8.26−8.13 (m, 2H), 7.86−7.71 (m, 2H), 7.70− 7.58 (m, 2H); 13C{1H} NMR (100 MHz, DMSO-d6) δ 138.0, 137.5, 137.5, 135.2, 132.3, 126.8, 121.2 (q, J = 322.5 Hz), 115.9, 115.1; HRMS (ESI) calcd for C12H8BrClI [M − OTf]+ 392.8537, found 392.8553. (4-Nitrophenyl)(phenyl)iodonium Trifluoromethanesulfonate (3w).2c GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as yellow solids (1.76 g, 74%): mp 178−183 °C (lit.2c 180−185 °C); 1H NMR (400 MHz, DMSO-d6) δ 8.51−8.45 (m, 2H), 8.35−8.27 (m, 4H), 7.74− 7.65 (m, 1H), 7.61−7.50 (m, 2H); 13C{1H} NMR (101 MHz, DMSOd6) δ 149.4, 136.4, 135.5, 132.4, 131.96, 126.3, 122.6, 120.7 (q, J = 322.4 Hz), 116.9. Mono(3-(p-tolyliodonio)pyridin-1-ium) Bis(trifluoromethanesulfonate) (3x).2c GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as light yellow solids (1.40 g, 47%): mp 163−167 °C (lit.2c 170−172 °C); 1H NMR (400 MHz, DMSO-d6) δ 9.27 (d, J = 2.2 Hz, 1H), 8.82 (dd, J = 4.7, 1.4 Hz, 1H), 8.64 (dt, J = 8.2, 1.8 Hz, 1H), 8.26−8.07 (m, 2H), 7.58 (dd, J = 8.2, 4.7 Hz, 1H), 7.36 (d, J = 8.1 Hz, 2H), 2.35 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 153.4, 152.1, 142.9, 142.3, 135.3, 132.5, 126.9, 120.7 (q, J = 323.3 Hz), 116.2, 113.0, 20.9. Mesityl(4-(trifluoromethyl)phenyl)iodonium Trifluoromethanesulfonate (3y). GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as brown solids (1.03 g, 38%): mp 202−205 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.14 (d, J = 8.3 Hz, 2H), 7.87 (d, J = 8.4 Hz, 2H), 7.25 (s, 2H), 2.59 (s, 6H), 2.31 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 143.5, 141.74, 135.0, 131.8, 129.9, 128.4 (d, J = 3.7 Hz), 124.7, 122.6, 120.5 (q, J = 295.3 Hz), 118.7, 26.3, 20.5; 19F NMR (376 MHz, DMSO-d6) δ −61.68, −77.75; HRMS (ESI) calcd for C16H15F3I [M − OTf]+ 391.0165, found 391.0183. (4-Chlorophenyl)(mesityl)iodonium Trifluoromethanesulfonate (3z).20 GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as light gray solids (2.21 g, 87%): mp 161−163 °C (lit.20 132−133 °C); 1H NMR (400 MHz, CDCl3) δ 7.67−7.60 (m, 2H), 7.40−7.34 (m, 2H), 7.11 (s, 2H), 2.62 (s, 6H), 2.36 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 144.8, 142.6, 138.9, 134.4, 132.5, 130.6, 120.9, 120.8 (q, J = 237.7 Hz), 108.9, 27.2, 21.3. (4-Bromophenyl)(mesityl)iodonium Trifluoromethanesulfonate (3aa).20 GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as light gray solids (2.48 g, 90%): mp 187−190 °C (lit.20 179−180 °C); 1H NMR (400 MHz, CDCl3) δ 7.57 (d, J = 8.8 Hz, 2H), 7.50 (d, J = 8.8 Hz, 2H), 7.09 (s, 2H), 2.61 (s, 6H), 2.34 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 144.6, 142. 6, 135.3, 134.7, 130.5, 126.9, 120.9, 120.3 (q, J = 319.9 Hz), 109.9, 27.2, 21.3. (4-(Ethoxycarbonyl)phenyl)(mesityl)iodonium Triflate (3ab).20 GP2 was used on a 5 mmol scale. Purification by recrystallization in

diethyl ether afforded the product as gray solids (1.39 g, 51%): mp 173−175 °C (lit.20 178−179 °C); 1H NMR (399 MHz, CDCl3) δ 8.01 (d, J = 8.6 Hz, 2H), 7.76 (d, J = 8.7 Hz, 2H), 7.11 (d, J = 1.0 Hz, 2H), 4.36 (q, J = 7.1 Hz, 2H), 2.61 (s, 6H), 2.36 (s, 3H), 1.36 (t, J = 7.1 Hz, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 164.9, 144.8, 142.7, 133.7, 132.9, 132.8, 130.5, 120.7, 120.3 (q, J = 319.9 Hz), 116.5, 62.0, 27.2, 21.3, 14.3. (4-Acetylphenyl)(mesityl)iodonium Trifluoromethanesulfonate (3ac).21 GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as gray solids (2.03 g. 79%): mp 183−184 °C (lit.21 183−185 °C); 1H NMR (399 MHz, CDCl3) δ 7.94 (d, J = 8.7 Hz, 2H), 7.79 (d, J = 8.7 Hz, 2H), 7.14 (s, 2H), 2.62 (s, 6H), 2.59 (s, 3H), 2.38 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 196.3, 145.1, 142.8, 139.6, 133.0, 131.6, 130.7, 120.4, 116.6, 27.3, 26.8, 21.3. Mesityl(3-(trifluoromethyl)phenyl)iodonium Trifluoromethanesulfonate (3ad).20 GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether to afford the product as brown solids (1.24 g, 46%): mp 180−182 °C (lit.20 181−183 °C); 1H NMR (400 MHz, CDCl3) δ 7.94 (d, J = 8.4 Hz, 1H), 7.91 (s, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.54 (t, J = 8.0 Hz, 1H), 7.12 (s, 2H), 2.63 (s, 6H), 2.36 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 144.9, 142.7, 134.2 (d, J = 33.8 Hz), 132.5, 130.6, 129.8 (d, J = 4.0 Hz), 128.6 (d, J = 3.7 Hz), 123.9, 121.2, 121.0, 120.2 (q, J = 319.2 Hz), 112.1, 27.2 21.3; 19F NMR (376 MHz, CDCl3) δ −63.05, −78.53. Mesityl(3-nitrophenyl)iodonium Trifluoromethanesulfonate (3ae). GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as brown solids (1.19 g, 46%): mp 162−164 °C; 1H NMR (400 MHz, DMSO-d6) δ 8.82 (t, J = 2.0 Hz, 1H), 8.42 (ddd, J = 8.2, 2.2, 0.9 Hz, 1H), 8.18 (ddd, J = 8.0, 1.8, 0.9 Hz, 1H), 7.75 (t, J = 8.2 Hz, 1H), 7.26 (s, 2H), 2.61 (s, 6H), 2.32 (s, 3H); 13C{1H} NMR (101 MHz, DMSO-d6) δ 148.6, 143.6, 141.9, 139.7, 132.9, 130.0, 128.9, 126.4, 122.7, 120.7 (q, J = 322.1 Hz), 114.1, 26.4, 20.6; HRMS (ESI) calcd for C15H15INO2 [M − OTf]+ 368.0142, found 368.0154. (2-Chlorophenyl)(mesityl)iodonium Trifluoromethanesulfonate (3af).21 GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as brown solids (1.24 g, 49%): mp 171−172 °C (lit.21 167−168 °C); 1H NMR (399 MHz, CDCl3) δ 7.62 (dd, J = 8.0, 1.5 Hz, 1H), 7.53 (td, J = 7.7, 1.4 Hz, 1H), 7.29 (td, J = 7.8, 7.4, 1.5 Hz, 1H), 7.17 (s, 2H), 7.09 (dd, J = 8.2, 1.4 Hz, 1H), 2.62 (s, 6H), 2.40 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 145.4, 143.0, 135.5, 133.5, 132.5, 131.4, 131.0, 130.6, 120.8, 120.4 (q, J = 319.9 Hz), 112.5, 27.2, 21.3. (2-Bromophenyl)(mesityl)iodonium Trifluoromethanesulfonate (3ag).21 GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as brown solids (1.54 g, 56%): mp 172−173 °C (lit.21 167−168 °C); 1H NMR (399 MHz, CDCl3) δ 7.74 (dd, J = 8.0, 1.5 Hz, 1H), 7.46 (td, J = 7.7, 1.5 Hz, 1H), 7.33 (ddd, J = 8.9, 7.5, 1.5 Hz, 1H), 7.20 (s, 2H), 6.86 (dd, J = 8.2, 1.4 Hz, 1H), 2.61 (s, 6H), 2.41 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 145.6, 143.0, 134.6, 133.3, 131.5, 131.2, 131.0, 124.7, 121.6, 120.4 (q, J = 319.8 Hz), 115.4, 27.2, 21.4. Mesityl(2-(trifluoromethyl)phenyl)iodonium Trifluoromethanesulfonate (3ah).21 GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as brown solids (891 mg, 33%): mp 176−178 °C (lit.21 180−181 °C); 1H NMR (400 MHz, CDCl3) δ 7.96−7.89 (m, 1H), 7.71 (t, J = 7.6 Hz, 1H), 7.54 (td, J = 7.8, 1.6 Hz, 1H), 7.28 (d, J = 8.0 Hz, 1H), 7.19 (s, 2H), 2.62 (s, 6H), 2.41 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 145.9, 143.1, 135.8, 133.1, 132.2, 131.4, 131.1, 129.6 (d, J = 4.8 Hz), 124.1, 121.9, 120.1 (q, J = 264.9 Hz), 107.5, 27.2, 21.4; 19F NMR (376 MHz, CDCl3) δ −59.93, −78.44. 3-(Mesityliodonio)pyridin-1-ium Bis(trifluoromethanesulfonate) (3ai).2c GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as light yellow solids (592 mg, 19%): mp 155−158 °C (lit.2c 138−141 °C); 1H NMR (400 MHz, DMSO-d6) δ 9.06 (d, J = 2.3 Hz, 1H), 8.79 (dd, J = 4.8, 1.3 Hz, 1H), 8.42 (d, J = 8.4 Hz, 1H), 7.55 (dd, J = 8.3, 4.7 Hz, 1H), 7.23 (s, 2H), 2.61 (s, 6H), 2.30 (s, 3H); 13C{1H} NMR (101 MHz, 11740

DOI: 10.1021/acs.joc.7b01346 J. Org. Chem. 2017, 82, 11735−11741

Article

The Journal of Organic Chemistry DMSO-d6) δ 152.9, 151.9, 143.3, 142.1, 141.6, 129.9, 127.1, 122.6, 120.7 (q, J = 322.4 Hz), 114.2, 26.3, 20.5. Mesityl(4-nitrophenyl)iodonium Trifluoromethanesulfonate (3aj).20 GP2 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as brown solids (827 mg, 32%): mp 197−200 °C (lit.20 208 °C); 1H NMR (399 MHz, DMSO-d6) δ 8.26 (d, J = 8.4 Hz, 2H), 8.22−8.12 (m, 2H), 7.26 (s, 2H), 2.59 (s, 6H), 2.31 (s, 3H); 13C{1H} NMR (100 MHz, DMSOd6) δ 149.3, 143.6, 141.8, 135.5, 130.0, 126.2, 122.8 (q, J = 201.9 Hz), 26.3, 20.6. o-Tolyl(p-tolyl)iodonium Trifluoromethanesulfonate (3ak).11b GP3 was used on a 4 mmol scale. Purification by recrystallization in diethyl ether afforded the product as brown solids (ortho−para 90%, para−para 5%, ortho−ortho 5%, 770 mg, 42%): mp 158−160 °C; 1H NMR (400 MHz, CDCl3) δ 8.09 (dd, J = 8.1, 1.2 Hz, 1H), 7.85−7.71 (m, 2H), 7.52 (td, J = 7.5, 1.2 Hz, 1H), 7.43 (dd, J = 7.7, 1.7 Hz, 1H), 7.22 (t, J = 5.4 Hz, 3H), 2.60 (s, 3H), 2.37 (s, 3H); 13C{1H} NMR (101 MHz, CDCl3) δ 143.4, 141.4, 137.6, 134.7, 133.5, 133.2, 132.1, 129.8, 120.4 (q, J = 320.0 Hz), 119.0, 109.0, 25.8, 21.5. Bis(4-(tert-butyl)phenyl)iodonium Trifluoromethanesulfonate (3al).22 GP3 was used on a 4 mmol scale. Purification by recrystallization in diethyl ether afforded the product as white needles (1.52 g, 70%): mp 163−165 °C (lit.22 164−165 °C); 1H NMR (400 MHz, CDCl3) δ 7.87−7.76 (m, 4H), 7.43−7.36 (m, 4H), 1.23 (s, 18H); 13C{1H} NMR (101 MHz, CDCl3) δ 156.7, 134.8, 129.7, 120.3 (d, J = 321.3 Hz), 109.4, 35.3, 31.0. Bis(2,5-dimethylphenyl)iodonium Trifluoromethanesulfonate (3am).11b GP3 was used on a 5 mmol scale. Purification by recrystallization in diethyl ether afforded the product as brown solids (896 mg, 46%): mp 168−169 °C (lit.11b 173−175 °C); 1H NMR (399 MHz, CDCl3) δ 7.73 (s, 2H), 7.33 (s, 4H), 2.56 (s, 6H), 2.34 (s, 6H); 13 C{1H} NMR (100 MHz, CDCl3) δ 140.6, 138.1, 136.9, 134.4, 132.0, 117.0, 25.1, 20.8.

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b01346. Description of reaction setups, optimization of reaction conditions and enthalpy measurements and spectral data of all products (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Volker Hessel: 0000-0002-9494-1519 Timothy Noël: 0000-0002-3107-6927 Author Contributions †

G.L. and H.P.L.G. contributed equally to this work.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Financial support is provided by the Dutch Science Foundation (NWO) by an ECHO grant (Grant No. 713.013.001) and a VIDI grant for T.N. (Grant No. 14150).

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REFERENCES

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DOI: 10.1021/acs.joc.7b01346 J. Org. Chem. 2017, 82, 11735−11741